Ibuprofen

Description

Ibuprofen Tablets, USP contain the active ingredient Ibuprofen, USP, which is chemically defined as (±) -2 - (p - isobutylphenyl) propionic acid. Ibuprofen appears as a white powder with a melting point ranging from 74° C to 77° C. It is characterized by very slight solubility in water (less than 1 mg/mL) and is readily soluble in organic solvents such as ethanol and acetone. The structural formula of Ibuprofen is represented below: Ibuprofen Structure Image.

This nonsteroidal anti-inflammatory drug (NSAID) is formulated for oral administration and is available in tablet strengths of 400 mg, 600 mg, and 800 mg. The tablets contain several inactive ingredients, including carnauba wax, colloidal silicon dioxide, croscarmellose sodium, microcrystalline cellulose, polysorbate 80, povidone, pregelatinized starch, sodium starch glycolate, stearic acid, hypromellose, polyethylene glycol, and propylene glycol.

Uses and Indications

Ibuprofen tablets are indicated for the relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Additionally, these tablets are indicated for the relief of mild to moderate pain and for the treatment of primary dysmenorrhea.

Limitations of Use: Controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in children have not been conducted. Therefore, the use of ibuprofen in pediatric populations should be approached with caution.

Dosage and Administration

Healthcare professionals should carefully consider the potential benefits and risks of Ibuprofen tablets and other treatment options before initiating therapy. It is recommended to use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

After assessing the response to initial therapy with Ibuprofen tablets, the dose and frequency should be adjusted to meet the individual needs of the patient. The total daily dose should not exceed 3,200 mg. In cases where gastrointestinal complaints arise, it is advisable to administer Ibuprofen tablets with meals or milk to mitigate these effects.

For the management of rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease, the suggested dosage ranges from 1,200 mg to 3,200 mg daily, administered as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). The dosage should be tailored to each patient, with adjustments made based on the severity of symptoms at the initiation of therapy or in response to treatment.

In the case of mild to moderate pain, a dosage of 400 mg may be administered every 4 to 6 hours as necessary for pain relief.

For the treatment of dysmenorrhea, Ibuprofen tablets should be administered at the onset of pain, with a recommended dose of 400 mg every 4 hours as needed for relief.

The smallest effective dose that provides acceptable control should always be employed to ensure optimal patient outcomes.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, the use of ibuprofen tablets is not recommended for patients who have a history of asthma, urticaria, or allergic-type reactions following the administration of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), as severe, potentially fatal, anaphylactic-like reactions have been reported in these individuals. Furthermore, ibuprofen tablets are contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen tablets, are associated with an increased risk of serious cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is likely to escalate with prolonged use. It is crucial to note that Ibuprofen tablets are contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

NSAIDs, including Ibuprofen tablets, can lead to severe gastrointestinal (GI) adverse events, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which may be fatal. These serious adverse events can occur at any time, with or without warning symptoms. Physicians should remain vigilant for signs or symptoms of GI bleeding, particularly in patients on long-term NSAID therapy.

Anaphylactoid reactions have been reported in patients without prior exposure to Ibuprofen tablets. In such cases, emergency medical assistance should be sought immediately. Additionally, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been documented in patients taking NSAIDs. If any signs or symptoms indicative of DRESS are observed, Ibuprofen tablets should be discontinued, and the patient should be evaluated without delay.

In pregnant women, the use of NSAIDs, including Ibuprofen tablets, is discouraged around 30 weeks of gestation and later due to the risk of premature closure of the fetal ductus arteriosus. Furthermore, the administration of NSAIDs at approximately 20 weeks of gestation or later may result in fetal renal dysfunction, potentially leading to oligohydramnios and, in some instances, neonatal renal impairment.

Ibuprofen tablets are not intended to replace corticosteroids or to manage corticosteroid insufficiency. Abrupt cessation of corticosteroids may precipitate disease exacerbation. It is also important to recognize that the pharmacological effects of Ibuprofen tablets in reducing fever and inflammation may obscure diagnostic signs that are critical for identifying complications in presumed noninfectious, painful conditions.

For patients on long-term NSAID treatment, periodic monitoring of complete blood count (CBC) and chemistry profiles is recommended. If clinical signs or symptoms consistent with liver or renal disease develop, or if abnormal liver tests persist or worsen, the use of Ibuprofen tablets should be discontinued.

Side Effects

Patients may experience a range of adverse reactions associated with the use of this medication, categorized by seriousness and frequency.

Serious adverse reactions include cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. The risk of these events may increase with the duration of use and can occur early in treatment. Additionally, there is an increased risk of serious gastrointestinal events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal complications can occur at any time during treatment and may present without warning symptoms, particularly in elderly patients who are at greater risk.

Common gastrointestinal adverse reactions reported include nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Other gastrointestinal issues may involve nausea and vomiting, indigestion, constipation, abdominal cramps or pain, and fullness of the gastrointestinal tract, characterized by bloating and flatulence. Serious gastrointestinal complications such as gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, gastritis, hepatitis, jaundice, abnormal liver function tests, and pancreatitis have also been observed.

Central nervous system reactions may include dizziness, headache, and nervousness, with more severe effects such as paresthesias, hallucinations, dream abnormalities, depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis with fever and coma. Pseudotumor cerebri has also been reported.

Dermatologic reactions can range from rash (including maculopapular types) and pruritus to more severe conditions such as vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia, toxic epidermal necrolysis, and photoallergic skin reactions.

Adverse reactions affecting special senses include tinnitus, hearing loss, amblyopia (blurred and/or diminished vision), conjunctivitis, diplopia, optic neuritis, and cataracts.

Hematologic reactions may manifest as anemia, neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, and decreases in hemoglobin and hematocrit. Bleeding episodes, such as epistaxis and menorrhagia, have also been reported.

Metabolic and endocrine reactions include decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis. Cardiovascular reactions may involve edema, fluid retention (which generally responds promptly to drug discontinuation), congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias (including sinus tachycardia and sinus bradycardia).

Allergic reactions can present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Other allergic conditions may include serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema.

Renal adverse reactions may include acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, hematuria, and renal papillary necrosis. Miscellaneous reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis.

Postmarketing experience has revealed additional skin and appendage reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and fixed drug eruption.

Drug Interactions

Concomitant use of ACE-inhibitors and NSAIDs may lead to a reduction in the antihypertensive effect of the ACE-inhibitors. This interaction warrants careful consideration in patients who are prescribed both classes of medications. Monitoring of blood pressure is advised in these patients to ensure therapeutic efficacy is maintained. Adjustments to the dosage of either medication may be necessary based on clinical response and blood pressure readings.

Packaging & NDC

The table below lists all NDC Code configurations of Ibuprofen, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of Ibuprofen tablets in pediatric patients have not been established. Therefore, caution should be exercised when considering the use of this medication in children. Further studies are needed to determine appropriate dosing and outcomes in this population.

Geriatric Use

Caution should be exercised when treating elderly patients (65 years and older) with this medication, as with any nonsteroidal anti-inflammatory drugs (NSAIDs). It is important for healthcare providers to consider the increased risk of adverse effects in this population. Monitoring for potential side effects and adjusting dosages as necessary may be warranted to ensure the safety and efficacy of treatment in geriatric patients.

Pregnancy

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen tablets, during pregnancy is associated with potential risks to the fetus. Specifically, the use of NSAIDs around 30 weeks of gestation or later increases the risk of premature closure of the fetal ductus arteriosus. Additionally, the use of NSAIDs at approximately 20 weeks of gestation or later has been linked to fetal renal dysfunction, which can lead to oligohydramnios and, in some cases, neonatal renal impairment.

Due to these risks, it is recommended that the use of Ibuprofen tablets be limited in dose and duration between approximately 20 and 30 weeks of gestation. If NSAID treatment is deemed necessary during this period, it should be restricted to the lowest effective dose for the shortest duration possible. Should treatment with Ibuprofen tablets extend beyond 48 hours, monitoring with ultrasound for oligohydramnios is advised. If oligohydramnios is detected, discontinuation of Ibuprofen tablets should occur, followed by appropriate clinical follow-up.

There are no adequate, well-controlled studies in pregnant women to establish the safety of Ibuprofen tablets. Therefore, the use of this medication in pregnancy should only be considered if the potential benefits justify the potential risks to the fetus. Published literature indicates that adverse outcomes, such as fetal renal dysfunction leading to oligohydramnios, may occur after days to weeks of NSAID treatment, although oligohydramnios has been reported as early as 48 hours after initiation. While many cases of decreased amniotic fluid were transient and reversible upon cessation of the drug, there have been limited reports of irreversible neonatal renal dysfunction requiring invasive interventions.

It is important to note that methodological limitations in postmarketing studies and reports, including the absence of control groups and limited data on dosage, duration, and timing of exposure, hinder the ability to reliably estimate the risk of adverse fetal and neonatal outcomes associated with maternal NSAID use. Furthermore, as the safety data primarily involve preterm infants, the applicability of these findings to full-term infants exposed to NSAIDs in utero remains uncertain.

Lactation

It is not known whether this drug is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants from Ibuprofen tablets, lactating mothers should consider the importance of the drug to their health when making a decision to either discontinue nursing or discontinue the drug.

Renal Impairment

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. Renal toxicity may occur in patients where renal prostaglandins play a compensatory role in maintaining renal perfusion. The use of NSAIDs can lead to a dose-dependent reduction in prostaglandin formation, which may subsequently decrease renal blood flow and precipitate overt renal decompensation.

Patients at greatest risk for these adverse effects include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. In cases where NSAID therapy is discontinued, recovery to the pretreatment state is typically observed.

There is no available information from controlled clinical studies regarding the use of Ibuprofen tablets in patients with advanced renal disease; therefore, treatment with Ibuprofen tablets is not recommended for these patients. If initiation of Ibuprofen tablet therapy is deemed necessary, close monitoring of the patient's renal function is advised.

Additionally, the use of NSAIDs, including Ibuprofen tablets, during pregnancy, particularly around 20 weeks gestation or later, may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some instances, neonatal renal impairment. Oligohydramnios may be reversible upon discontinuation of treatment. If NSAID treatment is required between approximately 20 and 30 weeks of gestation, it is recommended to limit the use of Ibuprofen tablets to the lowest effective dose for the shortest duration possible. Ultrasound monitoring of amniotic fluid should be considered if Ibuprofen tablet treatment extends beyond 48 hours, and the medication should be discontinued if oligohydramnios occurs, with follow-up conducted according to clinical practice.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when treated with NSAIDs, including Ibuprofen tablets. Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury, particularly in individuals where renal prostaglandins play a compensatory role in maintaining renal perfusion. In patients with compromised liver function, the administration of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate renal decompensation.

Patients at the highest risk for these adverse reactions include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. Due to the lack of controlled clinical study data regarding the use of Ibuprofen tablets in patients with advanced renal disease, treatment with Ibuprofen is not recommended for this population. If therapy with Ibuprofen tablets is deemed necessary, close monitoring of renal function is advised to mitigate the risk of renal complications. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state.

Overdosage

Approximately 1.5 hours following the ingestion of 7 to 10 ibuprofen tablets (400 mg) by a 19-month-old child weighing 12 kg, the patient presented to the hospital emergency room in a state of apnea and cyanosis, responding only to painful stimuli. This stimulus was sufficient to induce respiration. Upon admission, the child received oxygen and parenteral fluids, and a greenish-yellow fluid was aspirated from the stomach, revealing no evidence of ibuprofen. Two hours post-ingestion, the child's condition appeared stable; however, she continued to respond solely to painful stimuli and experienced apnea lasting 5 to 10 seconds. The patient was subsequently admitted to intensive care, where sodium bicarbonate, along with infusions of dextrose and normal saline, was administered. By four hours after ingestion, the child could be easily aroused, sit independently, and respond to verbal commands. A blood level of ibuprofen measured 102.9 µg/mL approximately 8.5 hours post-ingestion, and by 12 hours, the child showed complete recovery.

In two additional reported cases involving children, each weighing approximately 10 kg, accidental acute ingestion of approximately 120 mg/kg of ibuprofen resulted in no signs of acute intoxication or late sequelae. In one instance, a blood level of 700 µg/mL was recorded 90 minutes after ingestion, which is about ten times the peak levels observed in absorption-excretion studies. A 19-year-old male who ingested 8,000 mg of ibuprofen over several hours experienced dizziness, with nystagmus noted during examination. Following hospitalization, the patient received parenteral hydration and underwent three days of bed rest, ultimately recovering without any reported sequelae.

In cases of acute overdosage, it is recommended that the stomach be emptied through vomiting or gastric lavage; however, it should be noted that little drug may be recovered if more than one hour has passed since ingestion. Given the acidic nature of ibuprofen and its urinary excretion, the administration of alkali and the induction of diuresis may be theoretically beneficial. Supportive measures should be implemented, and the use of oral activated charcoal may assist in reducing both the absorption and reabsorption of ibuprofen tablets.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen tablets, during pregnancy has been associated with several teratogenic effects. Administration of NSAIDs around 30 weeks gestation or later may increase the risk of premature closure of the fetal ductus arteriosus. Additionally, the use of these medications from approximately 20 weeks gestation onward has been linked to fetal renal dysfunction, which can lead to oligohydramnios and, in some instances, neonatal renal impairment. Observational studies investigating other potential embryofetal risks associated with NSAID use during the first or second trimesters have yielded inconclusive results.

Reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities; however, it is important to note that animal reproduction studies do not always predict human outcomes. Prostaglandins play a critical role in various reproductive processes, including endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, the administration of prostaglandin synthesis inhibitors, such as ibuprofen, has resulted in increased pre- and post-implantation loss. Furthermore, prostaglandins are essential for fetal kidney development, and published animal studies indicate that prostaglandin synthesis inhibitors can impair kidney development when administered at clinically relevant doses.

Due to the potential for non-teratogenic effects, it is advised to avoid the use of NSAIDs, including Ibuprofen tablets, in pregnant women at approximately 30 weeks gestation and later. If NSAID treatment is deemed necessary between 20 and 30 weeks gestation, it is recommended to limit the use of Ibuprofen tablets to the lowest effective dose for the shortest duration possible. In cases where treatment extends beyond 48 hours, ultrasound monitoring of amniotic fluid should be considered. Ibuprofen tablets should be discontinued if oligohydramnios is detected, with follow-up conducted according to clinical practice guidelines.

In animal pharmacology and toxicology studies, the use of NSAIDs has been associated with adverse outcomes such as increased incidence of dystocia, delayed parturition, and decreased pup survival in rats. The effects of Ibuprofen tablets on labor and delivery in pregnant women remain unknown.

Postmarketing Experience

During post-approval use of ibuprofen, the following adverse reactions have been identified. These reactions have been reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and appendages-related adverse reactions include exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID, such as Ibuprofen tablets, and periodically throughout the course of treatment. They should be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

Healthcare providers should advise patients to be vigilant for symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately.

Patients should be made aware that Ibuprofen tablets, like other NSAIDs, can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects such as ulcers and bleeding, which may lead to hospitalization or even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis. They should be apprised of the importance of seeking medical advice upon observing any indicative signs or symptoms.

Patients should be instructed to stop taking Ibuprofen tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible.

Healthcare providers should also advise patients to be alert for symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or edema, and to contact their healthcare provider if such symptoms occur.

Patients should be informed about the warning signs and symptoms of hepatotoxicity, which may include nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms. If these symptoms occur, patients should be instructed to stop therapy and seek immediate medical attention.

Patients should be made aware of the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. If these symptoms occur, patients should be instructed to seek immediate emergency help.

Pregnant women should be informed to avoid the use of Ibuprofen tablets and other NSAIDs starting at 30 weeks gestation due to the risk of premature closure of the fetal ductus arteriosus. If treatment with Ibuprofen tablets is necessary for a pregnant woman between approximately 20 to 30 weeks gestation, she should be advised that monitoring for oligohydramnios may be required if treatment continues for longer than 48 hours.

Healthcare providers should monitor patients for signs or symptoms of GI bleeding, as serious GI tract ulcerations and bleeding can occur without warning symptoms. Patients on long-term treatment with NSAIDs should have their complete blood count (CBC) and chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash), or if abnormal liver tests persist or worsen, Ibuprofen tablets should be discontinued.

Storage and Handling

The product is supplied in accordance with the following specifications. It should be stored at a temperature range of 20º to 25ºC (68º to 77ºF), with permissible excursions between 15º to 30ºC (59º to 86ºF) as defined by USP Controlled Room Temperature guidelines. It is essential to avoid exposure to excessive heat, specifically temperatures exceeding 40ºC (104ºF). Proper storage conditions are critical to maintaining the integrity and efficacy of the product.

Additional Clinical Information

Clinicians are advised to monitor patients for signs or symptoms of gastrointestinal (GI) bleeding, as serious ulcerations and bleeding may occur without warning. For patients undergoing long-term treatment with NSAIDs, periodic checks of complete blood count (CBC) and chemistry profiles are recommended. If patients exhibit clinical signs consistent with liver or renal disease, or if systemic manifestations such as eosinophilia or rash develop, or if abnormal liver tests persist or worsen, discontinuation of ibuprofen tablets is warranted.

In the postmarketing experience, several adverse reactions have been reported following the approval of ibuprofen, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Ibuprofen as submitted by Florida Pharmaceutical Products, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)